McIvor, J. A. P. | Search bioRxiv

bioRxiv2025

Redox-controlled dimerisation regulates ethylene biosynthesis

Ethylene is a central plant hormone that orchestrates growth, development, senescence, and stress responses. Because it is gaseous, ethylene must be synthesised on demand, yet the catalytic and regulatory mechanisms of its biosynthetic enzyme, 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), remain poorly understood. Here, using structural, biophysical, and computational analyses, we uncovered two principles: ACO catalysis relies on an induced-fit mechanism, and disulfide-mediated dimerisation via a conserved cysteine acts as a redox switch toggling ACO between active monomer and inactive dimer. This previously unrecognised regulatory layer positions ACO as a redox sensor in plant cells, revealing a fundamental control point in ethylene biosynthesis. Given ethylenes pivotal role in crop productivity and stress resilience, these findings open new opportunities for precise manipulation of hormone signalling in agriculture and biotechnology.

biochemistry↗

bioRxiv2023

DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2

More than 1600 human transcription factors orchestrate the transcriptional machinery to control gene expression and cell fate. Their function is conveyed through intrinsically disordered regions (IDRs) containing activation or repression domains but lacking quantitative structural ensemble models prevents their mechanistic decoding. Here we integrate single-molecule FRET and NMR spectroscopy with molecular simulations showing that DNA binding can lead to complex changes in the IDR ensemble and accessibility. The C-terminal IDR of pioneer factor Sox2 is highly disordered but its conformational dynamics are guided by weak and dynamic charge interactions with the folded DNA binding domain. Both DNA and nucleosome binding induce major rearrangements in the IDR ensemble without affecting DNA binding affinity. Remarkably, interdomain interactions are redistributed in complex with DNA leading to variable exposure of two activation domains critical for transcription. Charged intramolecular interactions allowing for dynamic redistributions may be common in transcription factors and necessary for sensitive tuning of structural ensembles.

biophysics↗